The overall aim of this project is to investigate the molecular physiology or normal and abnormal hemoproteins. This study will correlate the changes in chemical reaction rates and thermodynamic values for these reactions with the concentrations of polyvalent anions such as DPG and ATP and polyvalent cations such as calcium ion. The specific types of reactions to be studied include aggregation phenomena as well as classical ligand reactions. The hemoproteins on which these studies will be done include respiratory transport pigments such as hemoglobin and myoglobin and enzymes such as catalase, cytochrome and peroxidase. The physiochemical studies will include equilibrium state measurements using the techniques of light scattering, differential refractometry, ultra-violet, visible and infra-red spectroscopy, polarographic and potentiometric measurements. The reactions to be studied are those of the above named hemoproteins with a variety of ligands, such as, oxygen, nitric oxide, carbon monoxide, cyanide, azide and fluoride. These reactions will be studied as a function of DPG, ATP and divalent cation concentrations. In the course of this research new knowledge of the detailed genetic mechanisms in humans should also be discovered. With this new knowledge it may be possible in cases such as homozygous Sickle Cell anemia to treat the disease by a more rational approach through the alteration of the concentration of small polyvalent electrolytes inside the cell.